Fibrosis is a crippling, largely irreversible, outcome of many chronic inflammatory diseases of the lung and other tissues. The modulating forces controlling the abundance and organization of collagen in the lung in disease states is only dimly understood at present. These investigations analyze the effects of lymphocyte and monocyte mediators upon lung fibroblasts since these chronic inflammatory cells are found with such frequency in the vicinity of progressing fibrosis. Human peripheral blood lymphocytes and monocytes and subpopulations are variously stimulated or incubated without stimulation for the preparation of conditioned supernates containing factors which actively modify human fibroblast activities. Fibroblast monolayers are assayed by microscopy and by the use of various radioisotopic markers such as 3H-thymidine, 14C-proline and 3H-tryptophan to monitor viability and proliferation and to determine effects upon non-collagenous and collagenous protein synthesis and degradation. The contributions of relative populations of mononuclear cell types and the effects of various immune and non-immunologic stimuli upon these mononuclear cells are assayed for their effects on fibroblasts using varying concentrations of the evoked mononuclear cell supernates. Active factors are isolated by analytical and biochemical separation techniques. Factors which stimulate collagen synthesis are particularly under study.